INSTITUTE OF ECOLOGY AND ENVIRONMENTAL STUDIES OBAFEMI AWOLOWO UNIVERSITY, ILE-IFE

A

TERMPAPER

ON

ENVIRONMENTAL EPIDEMIOLOGY (IEC 668)

TITLED

SEQUELAE OF VIRAL HEPATITIS

SUBMITTED TO PROF. I.E OFOEZIE

BY

ADEDEJI OLUWATOSIN ADEWUSI SCP13/14/H/1393

APRIL, 2015

CHAPTER ONE

VIRAL HEPATITIS

1.0 INTRODUCTION

Viral hepatitis is liver inflammation due to a viral infection. It may present in acute (recent infection, relatively

rapid onset) or chronic forms. The most common causes of viral hepatitis are the five unrelated hepatotropic

viruses Hepatitis A, Hepatitis B,Hepatitis C, Hepatitis D, and Hepatitis E.

Hepatitis viruses

HAV HBV HCV HDV HEV

Transmission Enteral Parenteral Parenter

al Parenteral Enteral

Classification Picorna virus

Orthohepadn

a virus

Hepaci

virus

Delta virus Hepevirus

Genome +ssRNA dsDNA-RT +ssRNA −ssRNA +ssRNA

Antigens HBsAg,HBeAg Core

antigen

Delta

antigen

Incubation period 20–40 days 45–160 days 15–150

days

30–60

days 15–60 days

Severity/Chronicity mild; acute

occasionally

severe;

5–10%

chronic

subclinic

al; 70%

chronic

exacerbat

es

symptoms

of HBV;

chronic w/

HBV

normal patients, mild;

pregnant women,

severe; acute

Vaccine 10 year

protection

3 injections,

lifetime

protection

None

available

None

available

Investigational(approv

ed in China)

1.1 HEPATITIS A

Hepatitis A or infectious jaundice is caused by hepatitis A virus (HAV), a picornavirus transmitted by

the fecal-oral route often associated with ingestion of contaminated food. It causes an acute form of

hepatitis and does not have a chronic stage. The patient's immune system makes antibodies against HAV

that confer immunity against future infection. People with hepatitis A are advised to rest, stay hydrated and

avoid alcohol. A vaccine is available that will prevent HAV infection for up to 10 years. Hepatitis A can be

spread through personal contact, consumption of raw sea food or drinking contaminated water. This occurs

primarily in third world countries. Strict personal hygiene and the avoidance of raw and unpeeled foods can

help prevent an infection. Infected people excrete HAV with their faeces two weeks before and one week

after the appearance of jaundice. The time between the infection and the start of the illness averages 28

days (ranging from 15 to 50 days), and most recover fully within 2 months, although approximately 15%

ofsufferers may experience continuous or relapsing symptoms from six months to a year following

initial diagnosis.

Hepatitis A

Marker Detection Time Description Significance

Faecal HAV 2–4 weeks or

28days – Early detection

Ig M anti

HAV 4–12 weeks

Enzyme immunoassay for

antibodies During Acute Illness

Ig G anti HAV 5 weeks –

persistent

Enzyme immunoassay for

antibodies

Old infection or

Reinfection

1.2 HEPATITIS B

Hepatitis B is caused by hepatitis B virus, a hepadnavirus that can cause both acute and chronic hepatitis.

Chronic hepatitis develops in the 15% of adults who are unable to eliminate the virus after an initial infection.

Identified methods of transmission include blood (blood transfusion, now rare),

unsanitary tattoos, sexually (through sexual intercourseor through contact with blood or bodily fluids), or via

mother to child by breast feeding[ (minimal evidence of transplacental crossing). However, in about half of

cases the source of infection cannot be determined. Blood contact can occur by sharing syringes in

intravenous drug use, shaving accessories such as razor blades, or touching wounds on infected

persons. Needle-exchange programmes have been created in many countries as a form of prevention.

Patients with chronic hepatitis B have antibodies against hepatitis B, but these antibodies are not enough to

clear the infection of the affected liver cells. The continued production of virus combined with antibodies is a

likely cause of the immune complex disease seen in these patients. A vaccine is available that will prevent

infection from hepatitis B for life. Hepatitis B infections result in 500,000 to 1,200,000 deaths per year

worldwide due to the complications of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatitis B is

endemic in a number of (mainly South-East Asian) countries, making cirrhosis and hepatocellular carcinoma

big killers.

1.3 HEPATITIS C

Hepatitis C (originally "non-A non-B hepatitis") is caused by hepatitis C virus (HCV), an RNA virus that is a

member of the Flaviviridae family. HCV can be transmitted through contact with blood (including through

sexual contact if the two parties' blood is mixed) and can also cross the placenta. Hepatitis C usually leads to

chronic hepatitis, culminating in cirrhosis in some people. It usually remains asymptomatic for decades.

Patients with hepatitis C are susceptible to severe hepatitis if they contract either hepatitis A or B, so all

persons with hepatitis C should be immunized against hepatitis A and hepatitis B if they are not already

immune, and avoid alcohol. HCV viral levels can be reduced to undetectable levels by a combination

of interferon and the antiviral drug ribavirin. The genotype of the virus is the primary determinant of the rate

of response to this treatment regimen, with genotype 1 being the most resistant.

Hepatitis C is the most common chronic blood-borne infection in the United States.

Hepatitis C

Marker Detection

Time Description Significance Note

HCV-

RNA

1–3 weeks

or 21 days PCR

Demonstrates

presence or absence

of virus

Results may be intermittent

during course of infection.

Negative result is not indicative

of absence.

anti-

HCV 5–6 weeks

Enzyme

Immunoassay for

antibodies

Demonstrates past

or present infection

High false positive in those with

autoimmune disorders and

populations with low virus

prevalence.

ALT 5–6 weeks –

Peak in ALT

coincides with peak

in anti-HCV

Fluctuating ALT levels is an

indication of active liver

disease.

1.4 HEPATITIS D

The Hepatitis D virus (HDV) or hepatitis delta agent is similar to a viroid as it can only propagate in the

presence of the hepatitis B virus.

1.5 HEPATITIS E

The Hepatitis E virus (HEV), from the Hepeviridae family, produces symptoms similar to hepatitis A, although it

can take a fulminant course in some patients, particularly pregnant women; chronic infections may occur in

immune-compromised patients. It is more prevalent in the Indian subcontinent.

CHAPTER TWO

SEQUELAE OF VIRAL HEPATITIS

Hepatitis can progress to, or be complicated by other diseases. Some of these diseases, like fibrosis

and cirrhosis, are very common. Fortunately, other complications like liver failure are usually

prevented. Ten possible complications linked with hepatitis.

2.1 ACUTE LIVER FAILURE Acute liver failure (also called fulminant hepatic failure, or fulminant hepatitis in the most serious forms) is a rapidly developing medical emergency caused by cells of the liver being injured so quickly that the liver cannot repair itself fast enough. Such an event can cause the liver to stop working altogether, resulting in problems in other areas of the body. Liver failure is a serious, but uncommon, complication of hepatitis. Doctors use different terms to describe variations of liver failure, such as fulminant liver failure, fulminant hepatic failure or acute liver failure. Basically, the liver no longer functions and this leads to the body shutting down, and eventually, death. There are many specific causes of liver failure, but in general, failure results when the liver is so damaged that it is unable to keep up with the body's needs. Acute liver failure is different from acute hepatitis in that parts of the liver begin to die or no longer work. Because the liver is such a vital part of the body, when it is damaged, other organs are affected, too. The brain is one of the more important organs affected during liver failure and injury to it results in a condition called encephalopathy.

2.1.1 Causes

The exact cause of FHF is unknown. The following may increase your risk:

Autoimmune diseases may cause your body to attack and damage your liver cells.

Cancer metastasis is when cancer has spread and reached your liver from other parts of your body.

A viral infection may cause hepatitis. Hepatitis causes your liver to get inflamed (swollen). Hepatitis can lead to FHF.

Herbal supplements or medicines such as acetaminophen may cause FHF. Acetaminophen is used for fever or pain. If more than the recommended dosage of this medicine is taken, it may damage your liver. Certain herbal and diet supplements may also lead to FHF.

Other diseases such as Wilson disease or Reye syndrome may cause FHF. Heart failure, heat stroke, and blood vessel diseases such as Budd-Chiari syndrome can also cause FHF. Women with acute fatty liver during pregnancy are also at risk for FHF.

2.1.2 Signs and Symptoms

Abdominal and back pain

Changes in mood and sleeping habits

Trouble thinking clearly

Itchy skin and a swollen abdomen, feet, and legs

Light-coloured bowel movements and decreased or dark-colored urine

Loss of appetite, nausea, and vomiting

Fatigue and weakness

Yellowing of your skin, gums, and the whites of your eyes

Other conditions that may occur with FHF include:

Blood problems such as blood clots or disseminated intravascular coagulation (DIC) may occur with FHF. DIC is a condition that causes your blood to clot throughout your whole body.

Encephalopathy occurs when harmful substances, such as ammonia, build up and cause brain damage.

Heart and lung problems such as hypotension (decreased blood pressure) and pulmonary oedema (swollen lungs) may occur. You may also get respiratory distress syndrome, which causes damage to the small blood vessels in your lungs.

Infections, such as respiratory and urinary tract infections, may occur with FHF.

Other health problems such as kidney failure, hypoglycemia (decreased blood sugar level), and pancreatitis may occur. Pancreatitis is when your pancreas is inflamed (swollen). Your FHF may also cause adrenal insufficiency.

2.1.3 Diagnosis

A liver biopsy is a procedure to remove a small piece of your liver. It is sent to a lab for tests. Healthcare providers will numb the area and put a needle through the wall of your abdomen or between your ribs. The needle is put into the liver and a small piece is taken out.

Blood and urine tests may show infection and liver function. They may also be done to get information about your overall health.

An abdominal ultrasound uses sound waves to show pictures of your abdomen on a monitor.

A CT, or CAT scan, is a type of x-ray that is taken of your liver. You may be given contrast dye to help healthcare providers see your liver better. Tell the healthcare provider if you have ever had an allergic reaction to contrast dye.

2.1.4 Treatment

i) Medicines:

o Anticoagulants are a type of blood thinner medicine that helps prevent clots. Clots can cause strokes, heart attacks, and death.

o Antibiotics help treat or prevent a bacterial infection.

o Antivirals help treat or prevent a viral infection. Antiviral medicine may also be given to control symptoms of a viral infection that cannot be cured.

o Antioxidants may be given if your FHF is caused by too much acetaminophen.

o Steroids may be given to decrease inflammation.

o Laxatives may help reduce the amount of ammonia in your blood by drawing it into your colon. It then leaves your body in your bowel movements.

ii) Artificial liver support may be needed. A machine is used to clean your blood when your liver cannot. Chemicals and waste products are removed from your blood by a filtering machine. Your blood is passed through a filter and then returned to your body.

Plasmapheresis removes antibodies from your blood. Some of your blood will be removed through an IV. The blood is then put in a machine that spins and separates the red blood cells from the antibodies. The cleaned blood is then put back in your body through the IV.

Surgery may be needed. You may need a liver transplant if your liver is badly damaged. All or part of your damaged liver is removed or replaced with a healthy liver from a donor

2.2 FIBROSIS

One of the most common complications of chronic hepatitis is fibrosis, which is a type of scarring of the liver. The liver is damaged by constant inflammation and creates the scar tissue to repair itself. Unfortunately, this scar tissue keeps the liver from working as it once did. The good news is that if fibrosis is controlled in time and limited to a small part of the liver, the rest of the organ can work harder and keep up with the liver's functions. When the fibrosis becomes extensive, doctors describe this as cirrhosis. 2.2.1 Causes

Autoimmune hepatitis

Certain storage diseases and inborn errors of metabolism

o α 1 -Antitrypsin deficiency

o Copper storage diseases (eg, Wilson disease)

o Fructosemia

o Galactosemia

o Glycogen storage diseases (especially types III, IV, VI, IX, and X)

o Iron-overload syndromes (hemochromatosis)

o Lipid abnormalities (eg, Gaucher disease)

o Peroxisomal disorders (eg, Zellweger syndrome)

o Tyrosinemia

Congenital hepatic fibrosis

o Infections

o Bacterial (eg, brucellosis)

o Parasitic (eg, echinococcosis)

o Viral (eg, chronic hepatitis B or C*)

Nonalcoholic steatohepatitis (NASH)

Primary biliary cirrhosis

Primary sclerosing cholangitis

Disorders affecting hepatic blood flow

o Budd-Chiari syndrome

o Heart failure

o Hepatic veno-occlusive disease †

o Portal vein thrombosis

Drugs and chemicals: Alcohol, Amiodarone, Chlorpromazine, Isoniazid, Methotrexate,

Methyldopa, Oxyphenisatin,Tolbutamide

Mechanical obstruction

o Scarring due to prior liver surgery

o Bile duct strictures due to impacted gallstones

Sometimes caused by pyrrolizidine alkaloids, present in herbal products such as bush teas.

2.2.2 Pathophysiology

Activation of the hepatic perivascular stellate cells (Ito cells, which store fat) initiates fibrosis. These

and adjacent cells proliferate, becoming contractile cells termed myofibroblasts. These cells produce

excessive amounts of abnormal matrix (consisting of collagen, other glycoproteins, and glycans) and

matricellular proteins. Kupffer cells (resident macrophages), injured hepatocytes, platelets, and

leukocytes aggregate. As a result, reactive O 2 species and inflammatory mediators (e.g platelet-

derived growth factor, transforming growth factors, connective tissue growth factor) are released.

Thus, stellate cell activation results in abnormal extracellular matrix, both in quantity and

composition.

Myofibroblasts, stimulated by endothelin-1, contribute to increased portal vein resistance and

increase the density of the abnormal matrix. Fibrous tracts join branches of afferent portal veins and

efferent hepatic veins, bypassing the hepatocytes and limiting their blood supply. Hence, fibrosis

contributes both to hepatocyte ischemia (causing hepatocellular dysfunction) and portal

hypertension. The extent of the ischemia and portal hypertension determines how the liver is

affected. For example, congenital hepatic fibrosis affects portal vein branches, largely sparing the

parenchyma. The result is portal hypertension with sparing of hepatocellular function.

2.2.3 Symptoms and Signs

Hepatic fibrosis itself does not cause symptoms. Symptoms may result from the disorder causing

fibrosis or, once fibrosis progresses to cirrhosis, from complications of portal hypertension. These

symptoms include variceal bleeding, ascites, and portosystemic encephalopathy. Cirrhosis can result

in hepatic insufficiency and potentially fatal liver failure.

2.2.4 Diagnosis

Clinical evaluation

Sometimes blood tests and/or non-invasive imaging tests

Sometimes liver biopsy

Hepatic fibrosis is suspected if patients have known chronic liver disease (eg, chronic viral hepatitis C)

or if results of liver function tests are abnormal; in such cases, tests are done to check for fibrosis

and, if fibrosis is present, to determine its severity (stage). Knowing the stage of fibrosis can guide

medical decisions. For example, screening for hepatocellular carcinoma and for gastroesophageal

varices is indicated if cirrhosis is confirmed, but it is not indicated for mild or moderate fibrosis. Also,

if liver biopsy does not detect advanced fibrosis in patients with hepatitis C, many clinicians defer

treatment with interferons because they anticipate that more effective, less toxic drugs will be

available.

Tests used to stage fibrosis include non-invasive imaging tests, blood tests, liver biopsy, and newer

tests that assess liver stiffness.

Non-invasive imaging tests include ultrasonography, CT, and MRI and should include cross-sectional

views. These tests can detect evidence of cirrhosis and portal hypertension, such as splenomegaly

and varices. However, they are not sensitive for moderate or even advanced fibrosis if splenomegaly

and varices are absent. Although fibrosis may appear as altered echogenicity on ultrasonography or

heterogeneity of signal on CT, these findings are nonspecific and may indicate only liver parenchymal

fat.

Liver biopsy remains the gold standard for diagnosing and staging hepatic fibrosis and for diagnosing

the underlying liver disorder causing fibrosis. However, liver biopsy is invasive, resulting in a 10 to

20% risk of minor complications (eg, postprocedural pain) and a 0.5 to 1% risk of serious

complications (eg, significant bleeding). Also, liver biopsy is limited by sampling error and imperfect

inter observer agreement in interpretation of histologic findings. Thus, liver biopsy may not always be

done.

Blood tests include commercially available panels that combine indirect markers (eg, serum bilirubin)

and direct markers of hepatic function. Direct markers are substances involved in the pathogenesis of

extracellular matrix deposition or cytokines that induce extracellular matrix deposition. These panels

are best used to distinguish between 2 levels of fibrosis: absent to minimal vs moderate to severe;

they do not accurately differentiate between degrees of moderate to severe fibrosis. Therefore, if

fibrosis is suspected, one approach is to start with one of these panels and then do liver biopsy only if

the panel indicates that fibrosis is moderate to severe.

Tests that assess liver stiffness may be useful but are not yet commonly used clinically; they include

ultrasound elastography, MRI elastography, and acoustic radiation force impulse imaging. For these

tests, acoustic vibrations are applied to the abdomen with a probe. How rapidly these vibrations are

transmitted through liver tissue is measured—an indication of how stiff (i.e fibrosed) the liver is.

However, central obesity in a patient can decrease diagnostic accuracy, potentially limiting the

usefulness of these tests in developed nations such as the US where obesity and metabolic syndrome

are common.

Which tests are done may depend on the degree of clinical suspicion, based on clinical evaluation,

including liver function test results. For example, non-invasive blood tests may be used to determine

whether biopsy is indicated; in some of these cases, imaging tests may not be needed.

2.2.5 Treatment

Because fibrosis represents a response to hepatic damage, primary treatment should focus on the

cause (removing the basis of the liver injury). Such treatment may include eliminating hepatitis B

virus or hepatitis C virus in chronic viral hepatitis, abstaining from alcohol in alcoholic liver disease,

removing heavy metals such as iron in hemochromatosis or copper in Wilson disease, and

decompressing bile ducts in biliary obstruction. Such treatments may stop the fibrosis from

progressing and, in some patients, also reverse some of the fibrotic changes.

Treatments aimed at reversing the fibrosis are usually too toxic for long-term use (e.g,

corticosteroids, penicillamine) or have no proven efficacy (eg, colchicine). Other antifibrotic

treatments are under study. Simultaneous use of multiple antifibrotic drugs may eventually prove

most beneficial. Silymarin, present in milk thistle, is a popular alternative medicine used to treat

hepatic fibrosis. It appears to be safe but to lack efficacy.

2.3 CIRRHOSIS OF THE LIVER

Extensive fibrosis is called cirrhosis. Hepatitis C and alcoholic hepatitis are two very common causes of

cirrhosis, though there are many others. It is a slowly progressing disease in which healthy liver tissue is

replaced with scar tissue, eventually preventing the liver from functioning properly. The scar tissue blocks the

flow of blood through the liver and slows the processing of nutrients, hormones, drugs, and naturally

produced toxins. It also slows the production of proteins and other substances made by the liver.

According to the National Institutes of Health, cirrhosis is the 12th leading cause of death by disease.

2.3.1 Causes

Hepatitis C, fatty liver, and alcohol abuse are the most common causes of cirrhosis of the liver in the U.S., but

anything that damages the liver can cause cirrhosis, including:

Fatty liver associated with obesity and diabetes

Chronic viral infections of the liver (hepatitis types B, C, and D; Hepatitis D is extremely rare)

Blockage of the bile duct, which carries bile formed in the liver to the intestines, where it

helps in the digestion of fats; in babies, this can be caused by biliary atresia in which bile ducts

are absent or damaged, causing bile to back up in the liver. In adults, bile ducts may become

inflamed, blocked, or scarred, due to another liver disease called primary biliary cirrhosis.

Repeated bouts of heart failure with fluid backing up into the liver

Certain inherited diseases such as:

Cystic fibrosis

Glycogen storage diseases, in which the body is unable to process glycogen, a form of sugar

that is converted to glucose and serves as a source of energy for the body

Alpha 1 antitrypsin deficiency, an absence of a specific enzyme in the liver

Diseases caused by abnormal liver function, such as hemochromatosis, a condition in which

excessive iron is absorbed and deposited into the liver and other organs, and Wilson's disease,

caused by the abnormal storage of copper in the liver

Although less likely, other causes of cirrhosis include reactions to prescribed drugs, prolonged exposure to

environmental toxins, or parasitic infections.

2.3.2 Risk Group

Most people who drink large amounts of alcohol harm their livers in some way, but not all of these people get

cirrhosis of the liver. Women who are heavy drinkers are at higher risk than men. People who have hepatitis

B or hepatitis C are more likely to suffer liver damage from alcohol.

2.3.4 Symptoms

The symptoms of cirrhosis of the liver vary with the stage of the illness. In the beginning stages, there may not

be any symptoms. As the disease worsens, symptoms may include:

Loss of appetite

Lack of energy (fatigue), which may be debilitating

Weight loss or sudden weight gain

Bruises

Yellowing of skin or the whites of eyes (jaundice)

Itchy skin

Fluid retention (edema) and swelling in the ankles, legs, andabdomen (often an early sign)

A brownish or orange tint to the urine

Light colored stools

Confusion, disorientation, personality changes

Blood in the stool

Fever

2.3.5 Diagnosis

Cirrhosis of the liver is diagnosed through several methods:

Physical exam. During a physical exam, your doctor can observe changes in how your liver

feels or how large it is (a cirrhotic liver is bumpy and irregular instead of smooth).

Blood tests. If your doctor suspects cirrhosis, you will be given blood tests to find out if liver

disease is present.

Other tests. In some cases, other tests that take pictures of the liver are performed, such as a

computerized tomography (CT scan),ultrasound, or another specialized procedure called a

radioisotope liver/spleen scan.

Biopsy. Your doctor may decide to confirm the diagnosis by taking a sample of tissue (biopsy)

from the liver.

Surgery. In some cases, cirrhosis is diagnosed during surgery when the doctor is able to see

the entire liver. The liver also can be inspected through a laparoscope, a viewing device that is

inserted through a tiny incision in the abdomen.

2.3.6 Complications

Complications associated with cirrhosis of the liver include:

Variceal bleeding. Variceal bleeding is caused by portal hypertension, which is an increase in

the pressure within the portal vein (the large vessel that carries blood from the digestive

organs to the liver). This increase in pressure is caused by a blockage of blood flow through

the liver as a result of cirrhosis. Increased pressure in the portal vein causes other veins in the

body to enlarge (varices), such as those in the oesophagus and stomach, to bypass the

blockage. These varices become fragile and can bleed easily, causing severe hemorrhaging

and fluid in the abdomen.

Confused thinking and other mental changes (hepatic encephalopathy). Hepatic

encephalopathy most often occurs when cirrhosis has been present for a long time. Toxins

produced in our intestines are normally detoxified by the liver, but once cirrhosis occurs, the

liver cannot detoxify as well. Toxins get into the bloodstream and can cause confusion,

changes in behaviour, and even coma.

Other serious complications of cirrhosis of the liver include:

Kidney failure

Reduced oxygen in the blood

Diabetes

Changes in blood counts

Increased risk of infections

Excessive bleeding and bruising

Breast enlargement in men

Premature menopause

Loss of muscle mass

Most of these complications can initially be treated with medicines or dietary changes. Once treatment for

these complications becomes ineffective, a liver transplant is considered. Almost all of the complications can

be cured by liver transplantation; however, in many circumstances, careful management can reduce the

harmful effects of cirrhosis and delay or even prevent the need for a liver transplant.

2.3.7 Treatment

Although there is no cure for cirrhosis of the liver, there are treatments available that can stop or delay its

progress, minimize the damage to liver cells, and reduce complications.

The treatment used depends on the cause of cirrhosis of the liver.

For cirrhosis caused by alcohol abuse, the person must stop drinking alcohol to halt the

progression of cirrhosis.

If a person has hepatitis, the doctor may prescribe steroids or antiviral drugs to reduce liver

cell injury.

For people with cirrhosis caused by autoimmune diseases, Wilson's disease, or

hemochromatosis, the treatment varies.

Medications may be given to control the symptoms of cirrhosis. Edema (fluid retention) and ascites (fluid in

the abdomen) are treated, in part, by reducing salt in the diet. Drugs called diuretics are used to remove

excess fluid and to prevent edema from recurring. Diet and drug therapies can help improve the altered

mental function that cirrhosis can cause. Laxatives such as lactulose may be given to help absorb toxins and

speed their removal from the intestines.

Liver transplantation may be needed for some people with severe cirrhosis.

2.3.8 Prevention

There are several ways to reduce your risk of developing cirrhosis of the liver:

Don't abuse alcohol. If you do drink alcohol, limit how much you drink and how often.

Remember, it's not only the heavy drinker who gets cirrhosis. If you drink more than 2 drinks

a day, you are increasing your risk. A drink is a 5-oz glass of wine, a 12-oz can of beer, or a 1

1/2-oz portion of hard liquor.

Avoid high-risk sexual behavior such as unprotected sexual contact with multiple partners.

Be careful around synthetic chemicals, such as cleaning products and pesticides. If you come

into contact with chemicals often, wear protective clothing and a facemask.

Get vaccinated against hepatitis B.

Eat a well-balanced, low-fat diet high in fruits and vegetables and take vitamins.

Maintain a healthy weight, because excess body fat can cause fatty liver, which may lead to

liver disease.

2.4 CANCER OF THE LIVER

One of the complications of cirrhosis is liver cancer, which is usually two types. Hepatocellular carcinoma is a type of cancer that affects the liver cells. The other type is cholangiolar carcinoma, which affects the bile ducts.

Liver cancer is a condition that happens when normal cells in the liver become abnormal and grow out of control into cancer.

2.4.1 Causes

Most people who get liver cancer get it in the setting of chronic liver disease (long-term liver damage

calledcirrhosis), which scars the liver and increases the risk for liver cancer. Conditions that cause cirrhosis are alcohol use/abuse, hepatitis B, and hepatitis C.

The causes of liver cancer may be linked to environmental, dietary, or lifestyle factors. In Nov. 2014, researchers at the University of California, San Diego School of Medicine, found that long-term exposure to

triclosan, a common ingredient in soaps and detergents, causes liver fibrosis and cancer in laboratory mice. Although triclosan has not been proven to cause human liver cancer, it is currently under scrutiny by the FDA to determine whether it has negative health impacts.

2.4.2 Risk Factors

Incidence rates of hepatocellular cancer are rising in the United States due to increasing prevalence of cirrhosis caused by chronic hepatitis C and non-alcoholic fatty liverdisease.

Cirrhosis of the liver due to any cause is a risk factor for liver cancer. The risk factors for liver cancer in cirrhosis are being male, age 55 years or older, Asian or Hispanic ethnicity, family history in a first-degree

relative, obesity, hepatitis B and C, alcohol use, and elevated iron content in the blood.

Chronic hepatitis B infection even without cirrhosis is a risk factor for liver cancer.

2.4.3 Signs and Symptoms

Liver cancer causes no symptoms of its own. As the tumor grows, it may cause symptoms of pain in the right side of the abdomen or a feeling of fullness when eating. Some patients may have worsening of symptoms of chronic liver disease or cirrhosis, which often precedes the development of cancer of the liver. For example, patients may complain of unexplained weight loss, wasting (cachexia), decreased appetite, increased swelling of the feet and belly, and yellowing of the eyes and skin (jaundice).

2.4.4 Diagnosis

The best way to detect liver cancer is through surveillance ultrasound of the liver done every six months in a patient with a diagnosis of cirrhosis and to treat the liver cancer as soon as it is detected.

Once a suspicion of liver cancer arises, a physician will order one the following:

1. Blood tests: alfa-fetoprotein (AFP), which may be elevated in 70% of patients with liver cancer. AFP levels could be normal in liver cancer. A rising level of AFP is suspicious for liver cancer. Other labs tests include des-gamma-carboxy prothrombin, which can be elevated in most patients with liver cancer.

2. Imaging studies: Multiphasic helical CT scan and MRI with contrast of the liver are the preferred imaging for detecting the location and extent of blood supply to the cancer. If any imaging study is inconclusive, then an alternative imaging study or follow-up imaging study should be performed to help clarify the diagnosis. Lesions smaller than 1 cm are usually difficult to characterize.

3. Liver biopsy is performed to sample tissue from the lesion in the liver, which is analyzed by a

pathologist to confirm the suspected diagnosis of liver cancer. Liver biopsy is not needed in every case, especially if the imaging study and lab markers are characteristic for liver cancer. Risks of liver biopsy are infection, bleeding, or seeding of the needle track with cancer. Seeding is when cancer cells get on the needle used for a biopsy and spread to other areas touched by the needle. Liver biopsy of suspected liver cancer carries the added risk of seeding the liver biopsy needle track in 1%-3% of cases. If a liver biopsy is inconclusive, then a repeat imaging study is recommended at three- to six-month intervals.

2.4.5 Treatment

The treatment chosen depends upon how much the cancer has spread and the general health of the liver. For example, the extent of cirrhosis (scarring) of the liver can determine the treatment options for the cancer.

Similarly, the spread and extent of spread of cancer beyond the liver tissue plays an important part in treatment options.

Surgery: Liver cancer can be treated sometimes with surgery to remove the part of liver with cancer. Surgical options are reserved for smaller sizes of cancer tumors. Liver transplant: The doctor replaces the cancerous liver with a healthy liver from another person. It is usually used in very small unresectable (not able to be removed) liver tumors in patients with advanced cirrhosis. Ablation therapy: This is a procedure that can kill cancer cells in the liver without any surgery. The doctor can kill cancer cells using heat, laser, or injecting a special alcohol or acid directly into the cancer. This technique may be used in palliation when the cancer is unresectable.

Embolization: Blocking the blood supply to the cancer can be done using a procedure called embolization. This technique uses a catheter to inject particles or beads that can block blood vessels that feed the cancer. Starving the cancer of the blood supply prevents the growth of the cancer. This technique is usually used on patients with large liver cancer for palliation. Radiation therapy: Radiation uses high-energy rays directed to the cancer to kill cancer cells. Chemotherapy: Chemotherapy uses a medicine that kills cancer cells. The medicine can be given by mouth or by injecting it into a vein. Sorafenib is an oral medication that can prolong survival (up to 3 months) in patients with advanced liver cancer.

2.4.6 Treatment Follow up.

Patients are advised to follow up with the doctor for lab tests and office visits. Patients with chronic liver disease should avoid alcohol and any drugs that can harm the liver. Patients with liver transplants will need to take antirejection drugs for the rest of their life to prevent their body from rejecting the new liver.

2.4.7 Prevention

Prevention of cirrhosis, which is the underlying cause of liver cancer, will help in preventing the development of liver cancer.

Routine surveillance for liver cancer by performing ultrasound of the liver every six months in patients with a cirrhotic liver will detect early liver cancer.

2.5 GLOMERULONEPHRITIS

Glomerulonephritis is a complicated disorder of the kidneys caused by inflammation and is seen in chronic hepatitis B and hepatitis C infections. 2.5.1 Causes

Glomerulonephritis may be caused by problems with the body's immune system. Often, the exact cause of

glomerulonephritis is unknown.

Damage to the glomeruli causes blood and protein to be lost in the urine.

The condition may develop quickly, and kidney function is lost within weeks or months (called rapidly

progressive glomerulonephritis).

A quarter of people with chronic glomerulonephritis have no history of kidney disease.

The following may increase your risk of this condition:

Blood or lymphatic system disorders

Exposure to hydrocarbon solvents

History of cancer

Infections such as strep infections, viruses, heart infections, or abscesses

Many conditions cause or increase the risk for glomerulonephritis, including:

Amyloidosis

Anti-glomerular basement membrane antibody disease

Blood vessel diseases, such as vasculitis or polyarteritis

Focal segmental glomerulosclerosis

Goodpasture syndrome

Heavy use of pain relievers, especially NSAIDs

Henoch-Schonlein purpura

IgA nephropathy

Lupus nephritis

Membranoproliferative GN

2.5.2 Symptoms

Common symptoms of glomerulonephritis are:

Blood in the urine (dark, rust-colored, or brown urine)

Foamy urine (due to excess protein in the urine)

Swelling (edema) of the face, eyes, ankles, feet, legs, or abdomen

Symptoms may also include the following:

Abdominal pain

Blood in the vomit or stools

Cough and shortness of breath

Diarrhoea

Excessive urination

Fever

General ill feeling, fatigue, and loss of appetite

Joint or muscle aches

Nosebleed

The symptoms of chronic kidney disease may develop over time.

Chronic renal failure symptoms may gradually develop.

2.5.3 Diagnosis

Because symptoms may develop slowly, the disorder may be discovered when you have an

abnormal urinalysis during a routine physical or examination for another condition.

Signs of glomerulonephritis can include:

Anaemia

High blood pressure

Signs of reduced kidney function

A kidney biopsy confirms the diagnosis.

Later, signs of chronic kidney disease may be seen, including:

Nerve inflammation (polyneuropathy)

Signs of fluid overload, including abnormal heart and lung sounds

Swelling (oedema)

Imaging tests that may be done include:

Abdominal CT scan

Kidney ultrasound

Chest x-ray

Intravenous pyelogram (IVP)

Urinalysis and other urine tests include:

Creatinine clearance

Examination of the urine under a microscope

Urine for total protein

Uric acid in the urine

Urine concentration test

Urine creatinine

Urine protein

Urine RBC

Urine specific gravity

Urine osmolality

This disease may also cause abnormal results on the following blood tests:

Albumin

Anti-glomerular basement membrane antibody test

Anti-neutrophil cytoplasmic antibodies (ANCAs)

Anti-nuclear antibodies

BUN and creatinine

Complement levels

2.5.4 Treatment

Treatment depends on the cause of the disorder, and the type and severity of symptoms. High blood pressure

may be hard to control. Controlling high blood pressure is usually the most important part of treatment.

Medicines that may be prescribed include:

Blood pressure medications to control high blood pressure, most commonly angiotensin-

converting enzyme inhibitors and angiotensin receptor blockers

Corticosteroids

Medications that suppress the immune system

A procedure called plasmapheresis may sometimes be used for glomerulonephritis caused by immune

problems. The fluid part of the blood that contains antibodies is removed and replaced with intravenous fluids

or donated plasma (that does not contain antibodies). Removing antibodies may reduce inflammation in the

kidney tissues.

You may need to limit salt, fluids, protein, and other substances.

Persons with this condition should be closely watched for signs of kidney failure. Dialysis or a kidney

transplant may eventually be needed.

2.5.5 Prognosis

Glomerulonephritis may be temporary and reversible, or it may get worse. Progressive glomerulonephritis

may lead to:

Chronic kidney failure

Reduced kidney function

End-stage kidney disease

If you have nephrotic syndrome and it can be controlled, you may also be able to control other symptoms. If it

cannot be controlled, you may develop end-stage kidney disease.

2.5.6 Possible Complications

Acute nephritic syndrome

Blood electrolyte problems

Chronic kidney disease

Chronic or repeated urinary tract infection

End-stage kidney disease

Fluid overload -- congestive heart failure, pulmonary edema

Hyperkalemia

Hypertension

Increased susceptibility to other infections

Malignant hypertension

Nephrotic syndrome

2.5.7 Prevention

There is no way to prevent most cases of glomerulonephritis. Some cases may be prevented by avoiding or

limiting exposure to organic solvents, mercury, and nonsteroidal anti-inflammatory drugs (NSAIDs).

2.6 CRYOGLOBULINEMIA

Seen in chronic hepatitis B and hepatitis C infection, cryoglobulinemia is an uncommon disease caused by an

abnormal cluster of a kind of protein that blocks small blood vessels leading to circulation problems.

Cryoglobulinemia is the presence of abnormal proteins in the blood. These proteins thicken in cold

temperature.

2.6.1 Causes

Cryoglobulins are antibodies. It is not yet known why they become solid or gel-like at low temperatures. When

this occurs, these antibodies can block blood vessels. This may lead to problems ranging from skin rashes to

kidney failure.

Cryoglobulinemia is part of a group of diseases that cause damage and inflammation of the blood vessels

throughout the body (vasculitis). There are three main types of the disorder. They are grouped based on the

type of antibody that is produced:

Cryoglobulinemia type I

Cryoglobulinemia type II

Cryoglobulinemia type III

Types II and III are also referred to as mixed cryoglobulinemia.

Type I cryoglobulinemia is most often related to cancer of the blood or immune systems.

Types II and III are most often found in people who have a chronic (long-lasting) inflammatory condition, such

as an autoimmune disease or hepatitis C. Most people with mixed cryoglobulinemia have a chronic hepatitis C

infection.

Other conditions that may be related to cryoglobulinemia include:

Leukemia

Multiple myeloma

Mycoplasma pneumonia

Primary macroglobulinemia

Rheumatoid arthritis

Systemic lupus erythematosus

2.6.2 Symptoms

Symptoms will vary depending on the type of disorder you have and the organs that are involved. Symptoms

may include:

Breathing problems

Fatigue

Glomerulonephritis

Joint pain

Muscle pain

Purpura

Raynaud's phenomenon

Skin death

Skin ulcers

2.6.3 Diagnosis

Tests for cryoglobulinemia include:

Complete blood count (CBC)

Complement assay -- numbers will be low

Cryoglobulin test -- may show presence of cryoglobulins

Liver function tests -- may be high

Rheumatoid factor -- positive in types II and III

Skin biopsy

Urinalysis -- may show blood in the urine if the kidneys are affected

Other tests may include:

Angiogram

Chest x-ray

ESR

Hepatitis C test

Nerve conduction tests, if the person has weakness in the arms or legs

Protein electrophoresis - blood

2.6.3 Treatment

Mild or moderate forms of cryoglobulinemia can often be treated by taking steps to deal with

the underlying cause. Mild cases can be treated by avoiding cold temperatures.

Standard hepatitis C treatments usually work for patients who have hepetitis C and mild or

moderate disease. The condition can return when treatment stops.

Severe cryoglobulinemia involves vital organs or large areas of skin. It is treated with

corticosteroids and other medicines that calm the immune system.

Treatment may also involve plasmapheresis. In this procedure, blood plasma is taken out of blood circulation.

It is replaced by fluid, protein, or donated plasma.

2.6.4 Prognosis

Most of the time cryoglobulinemia is not usually deadly. Outlook can be poor if the kidneys are affected.

2.6.5 Possible Complications

Complications include:

Bleeding in the digestive tract (rare)

Heart disease (rare)

Infections of ulcers

Kidney failure

Liver failure

Skin death

Death

2.6.6 Prevention

There is no known prevention.

Staying away from cold temperatures may prevent some symptoms.

Testing and treatment for hepatitis C infection may reduce your risk of the condition.

2.7 HEPATIC ENCEPHALOPATHY

Severe loss of liver function, such as liver failure, can lead to inflammation in the brain called encephalopathy. This causes mental problems, like confusion, and can lead to coma. Advanced hepatic encephalopathy is a serious condition and is usually fatal. Hepatic encephalopathy is the loss of brain function that occurs when the liver is unable to remove toxins from the blood. 2.7.1 Causes The exact cause of hepatic encephalopathy is unknown. Hepatic encephalopathy is brought on by disorders that affect the liver. These include:

Conditions that reduce liver function (such as cirrhosis or hepatitis)

Conditions in which blood circulation does not enter the liver

An important job of the liver is to make toxic substances in the body harmless. These can include substances made by the body as well things that you take in (such as medicines). However, when the liver is damaged, these "poisons" can build up in the bloodstream. Ammonia, which is produced by the body when proteins are digested, is one of the substances normally made harmless by the liver. Other toxins may also build up. These things can cause damage to the nervous system.

When liver damage occurs, hepatic encephalopathy may occur suddenly, even in people who have not had liver problems in the past. More often, the problem develops in people with chronic liver disease.

Hepatic encephalopathy may be triggered by:

Dehydration

Eating too much protein

Electrolyte abnormalities (especially a decrease in potassium) from vomiting, or from treatments such as paracentesis or taking diuretics ("water pills")

Bleeding from the intestines, stomach, or oesophagus

Infections

Kidney problems

Low oxygen levels in the body

Shunt placement or complications

Surgery

Medicines that suppress the central nervous system (such as barbiturates or benzodiazepine tranquilizers)

Disorders that can appear similar to hepatic encephalopathy include:

Alcohol intoxication

Complicated alcohol withdrawal

Meningitis

Metabolic abnormalities such as low blood glucose

Sedative overdose

Subdural hematoma (bleeding under the skull)

Wernicke-Korsakoff syndrome

In some cases, hepatic encephalopathy is a short-term problem that can be corrected. It may also occur as part of a chronic problem from liver disease that gets worse over time. 2.7.2 Symptoms

Symptoms may begin slowly and slowly get worse. They may also begin suddenly and be severe from the

start.

Early symptoms may be mild and include:

Breath with a musty or sweet odour

Change in sleep patterns

Changes in thinking

Confusion that is mild

Forgetfulness

Mental fogginess

Personality or mood changes

Poor concentration

Poor judgment

Worsening of handwriting or loss of other small hand movements

More severe symptoms may include:

Abnormal movements or shaking of hands or arms

Agitation, excitement, or seizures (occur rarely)

Disorientation

Drowsiness or confusion

Strange behaviour or severe personality changes

Slurred speech

Slowed or sluggish movement

People with hepatic encephalopathy can become unconscious, unresponsive, and possibly enter a coma.

Patients are often not able to care for themselves because of these symptoms.

2.7.3 Diagnosis Signs of nervous system changes may include:

Shaking of the hands ("flapping") when trying to hold arms in front of the body and lift the hands

Problems with thinking and doing mental tasks

Signs of liver disease, such as yellow skin and eyes (jaundice) and fluid collection in the abdomen (ascites)

Musty odour to the breath and urine

Tests may include:

Complete blood count or hematocrit to check for anemia

CT scan of the head or MRI

EEG

Liver function tests

Prothrombin time

Serum ammonia levels

Sodium level in the blood

Potassium level in the blood

BUN and creatinine to see how the kidneys are working

2.7.4 Treatment

Hepatic encephalopathy can be a medical emergency that requires a hospital stay.

The first step is to identify and treat any factors that may have caused hepatic encephalopathy.

Gastrointestinal bleeding must be stopped. The intestines must be emptied of blood. Infections, kidney

failure, and electrolyte abnormalities (especially potassium) need to be treated.

Life support may be necessary to help with breathing or blood circulation, particularly if the person is in a

coma. The brain may swell, which can be life-threatening.

If the problem is very bad, you may need to cut down the protein in your diet. However, too little protein can

cause malnutrition, so you should talk to a dietitian about how to change your diet. People who are very ill

may need intravenous or tube feedings.

You may be given lactulose to prevent intestinal bacteria from creating ammonia and to remove blood from

the intestines. You may also get neomycin to reduce ammonia production by intestinal bacteria. Rifaximin, a

new antibiotic, is also effective in hepatic encephalopathy.

You may need to avoid sedatives, tranquilizers, and any other medicines that are broken down by the liver.

Medicines containing ammonium (including certain antacids) should also be avoided. Your doctor may suggest

other medicines and treatments. These may have varying results.

2.7.5 Prognosis

Acute hepatic encephalopathy may be treatable. Chronic forms of the disorder often continue to get worse

and come back.

Both forms of the condition may result in irreversible coma and death. The majority of people who go into a

coma will die. The chances of getting better vary from person to person.

2.7.6 Possible Complications

Brain herniation

Brain swelling

Increased risk of heart, kidney, and breathing problems

Increased risk of body-wide infection

Permanent nervous system damage

Coma that continues to get worse

Side effects of medicines

2.7.7 Prevention

Treating liver problems may prevent hepatic encephalopathy. Avoiding heavy drinking and intravenous drug

use can prevent many liver disorders.

2.8 PORTAL HYPERTENSION

One of the liver's important jobs is to filter blood. However, cirrhosis and other problems can interfere with the liver's portal circulation system. When this portal system is blocked, blood can't return to the liver from the digestive system and pressure increases, called portal hypertension. This is a serious complication and can be fatal.

Liver cirrhosis increases resistance to blood flow and higher pressure in the portal venous system, resulting

in portal hypertension. Effects of portal hypertension include:

Splenomegaly (increase in size of the spleen) is found in 35% to 50% of patients.

Esophageal varices result from collateral portal blood flow through vessels in the stomach and

esophagus (a process called Portacaval anastomosis). When these blood vessels become

enlarged, they are called varices and are more likely to burst.

Caput medusa are dilated periumbilical collateral veins due to portal hypertension. Blood from

the portal venous system may be shunted through the periumbilical veins and ultimately to the

abdominal wall veins, manifesting as a pattern that may resemble the head of Medusa.

Cruveilhier-Baumgarten murmur is a venous hum heard in the epigastric region (on examination

by stethoscope) due to collateral connections forming between portal system and the

periumbilical veins as a result of portal hypertension.

2.8.1 Causes

Causes can be divided into pre-hepatic, intra-hepatic, and post-hepatic.

Prehepatic causes include portal vein thrombosis or congenital atresia.

Intrahepatic causes include liver cirrhosis, hepatic fibrosis (e.g. due to Wilson's

disease, hemochromatosis, or congenital fibrosis), and less commonly noncirrhotic causes

such as schistosomiasis, massive fatty change and diffuse granulomatous diseases

(e.g.sarcoidosis, miliary tuberculosis).

Post hepatic obstruction occurs at any level between liver and right heart, including hepatic

vein thrombosis, inferior vena cava thrombosis, inferior vena cava congenital malformation,

and constrictive pericarditis.

2.8.2 Signs and Symptoms

Consequences of portal hypertension are caused by blood being forced down alternate channels by the

increased resistance to flow through the systemic venous system rather than the portal system. They include:

Ascites (free fluid in the peritoneal cavity).

Hepatic encephalopathy.

Increased risk of spontaneous bacterial peritonitis.

Increased risk of hepatorenal syndrome.

Splenomegaly (enlargement of the spleen) with a consequent accumulation of red blood

cells, white blood cells, and platelets, together leading to mildpancytopenia.

Development of varices at portacaval anastomoses: Esophageal varices, gastric

varices, anorectal varices (not to be confused with hemorrhoids), and caput medusae.

Esophageal and gastric varices pose an ongoing risk of life-threatening bleeding, with bloody

vomiting or melena.

2.8.3 Diagnosis

HVPG (hepatic venous pressure gradient) measurement has been accepted as the gold standard for assessing

the severity of portal hypertension, and replaced the old one - contrast angiography. Portal hypertension is

defined as HVPG greater than or equal to 5mm Hg and is considered to be clinically significant when HVPG

exceeds 10 to 12 mm Hg.

2.8.4 Treatment

Portosystemic Shunts

These can be categorized by several different concepts: selective vs non-selective, mesocaval vs portocaval,

and the specific arrangement of vessels, e.g. end-to-side or side-to-side. Selective shunts select non-intestinal

flow to be shunted to the systemic venous drainage while leaving the intestinal venous drainage to continue

pass through the liver. The most well known of this type is the splenorenal, or Warren, shunt. This connects

the splenic vein to the left renal vein thus reducing portal system pressure while minimizing any

encephalopathy. In an H-shunt, which could be mesocaval (from the superior mesenteric vein to the inferior

vena cava) or could be, unlikely, portocaval (from the portal vein to the inferior vena cava) a graft, either

synthetic or the preferred vein harvested from somewhere else on the patient's body, is connected between

the superior mesenteric vein and the inferior vena cava. The size of this shunt will determine how selective it

is.

It should be noted that with the advent of transjugular intrahepatic portosystemic shunting (TIPS),

portosystemic shunts are now very rarely performed. TIPS has the advantage of being much easier to perform

and it doesn't disrupt any of the liver's vascularity, which will be needed if a given patient's hopes for liver

transplant. In general, non-selective shunts are emergency surgeries that are done as quickly as possible to

minimize intraoperative blood loss. On the contrary, a splenorenal shunt would be an elective procedure due

to its great technical demands. Further contributing to their rare use today is the fact that few, if any, current

general surgery residents are trained in how to carry out these surgeries.

Prophylaxis of variceal bleeding

Both pharmacological (non-specific ß-blockers like Propranolol and isosorbide mononitrate) and endoscopic

(banding ligation) treatment have similar results. TIPS (transjugular intrahepatic portosystemic shunting) is

superior to either of them at reducing rate of rebleeding. Disadvantages of TIPS include high cost and

increased risk of hepatic encephalopathy, and it does not improve the mortality rate.

Management of active variceal bleeding

After resuscitation, which may require blood transfusion, the management of active variceal bleeding includes

administering vasoactive drugs (somatostatin, octreotide or terlipressin), endoscopic banding ligation, balloon

tamponade and TIPS (Transjugular intrahepatic portocaval shunt)

Management of ascites

This should be gradual to avoid sudden changes in systemic volume status which can precipitate hepatic

encephalopathy, renal failure and death. The management includes salt

restriction, diuretics (spironolactone), paracentesis, transjugular intrahepatic portosystemic shunt (TIPS)

and peritoneovenous shunt.

Control of hepatic encephalopathy

A standard treatment plan may involve lactulose, bowel enemas, and use of oral antibiotics such as rifaximin,

neomycin, metronidazole, vancomycin, and the quinolones. Previously, restriction of dietary protein was

recommended but this is now refuted by a clinical trial which showed no benefit. Instead, the maintenance of

adequate nutrition is now advocated.

2.9 PORPHYRIA

Porphyria is a group of diseases caused by problems processing important chemicals in the body called

porphyrins. One type, called porphyria cutanea tara, leads to blistering of the hands and face and is a rare

complication of chronic hepatitis C infection.

2.9.1 Causes

Porphyria is most often an inherited mutation in one of the genes involved in heme production, although

environmental factors can trigger symptoms in some cases.

Heme is a major component of haemoglobin, the protein in red blood cells that carries oxygen from your

lungs to all parts of your body. Heme also plays a role in breaking down chemicals so they can be removed

from your body. Heme is made mainly in the bone marrow and liver through the production of porphyrin and

linkage with iron.

Eight different enzymes add and convert natural, smaller building blocks into porphyrin, which becomes heme

with the addition of iron. Deficiency of a specific enzyme that's involved in the body's process for making

heme can result in the buildup of porphyrins, causing symptoms. Each type of porphyria is due to the

deficiency of a different enzyme.

2.9.2 Genetics

Most forms of porphyria are inherited. Porphyria can occur if you inherit:

A defective gene from one of your parents (autosomal dominant pattern)

Defective genes from both parents (autosomal recessive pattern)

Just because you have inherited a gene or genes that can cause porphyria doesn't mean that you'll have signs

and symptoms. You might have what's called latent porphyria, and never have symptoms. This is the case for

most carriers of the abnormal genes.

There are two general categories of porphyria — acute, which mainly affects the nervous system, and

cutaneous, which mainly affects the skin. Some types of porphyria have both nervous system symptoms and

skin symptoms, and others have mainly one or the other.

2.9.3 Symptoms

Acute porphyrias

Acute porphyrias include forms of the disease that typically cause nervous system symptoms, which appear

quickly and can be life-threatening. Acute porphyria attacks are rare before puberty and after menopause in

women. Symptoms may last one to two weeks and usually improve slowly after the attack.

Possible signs and symptoms of acute porphyria include:

Severe abdominal pain

Swelling of the abdomen (abdominal distention)

Pain in your chest, legs or back

Constipation or diarrhoea

Vomiting

Insomnia

Heartbeat you can feel (palpitations)

High blood pressure

Anxiety or restlessness

Seizures

Mental changes, such as confusion, hallucinations, disorientation or paranoia

Breathing problems

Muscle pain, tingling, numbness, weakness or paralysis

Red or brown urine

Cutaneous porphyrias

Cutaneous porphyrias include forms of the disease that cause skin symptoms as a result of oversensitivity to

sunlight, but these forms don't usually affect your nervous system. Attacks may last for several days. With

some forms, signs and symptoms may start during infancy or childhood.

As a result of sun exposure, you may experience:

Sensitivity to the sun and sometimes artificial light, causing burning pain

Sudden painful skin redness (erythema) and swelling (edema)

Blisters that take weeks to heal

Itching

Fragile skin

Scars or skin color changes from healing blisters

Increased hair growth

Red or brown urine

2.9.4 Risk Factors

In addition to genetic risks, environmental factors may trigger the development of signs and symptoms in

some types of porphyria. When exposed to the trigger, your body's demand for heme production increases.

This overwhelms the deficient enzyme, setting in motion a process that causes signs and symptoms. Examples

of triggers include:

Certain drugs (barbiturates or sulfonamide antibiotics or, less often, birth control pills, or

some drugs that affect the mind or behaviour, known as psychoactive drugs)

Chemicals

Dieting or fasting

Smoking

Physical stress, such as infections or other illnesses

Liver disease

Emotional stress

Alcohol use

Menstrual hormones

Sun exposure

Excess iron in your body

2.9.5 Complications

Possible complications of porphyria include:

Dehydration. Vomiting due to an attack of acute porphyria can lead to dehydration, which may

require that you receive fluids through a vein (intravenously).

Breathing difficulties. Acute porphyrias can cause muscle weakness and paralysis, which can

cause breathing problems. If left untreated, they can also lead to respiratory failure.

Low sodium in your blood. Called hyponatremia, this is usually linked to problems with sodium

and water handling in your body.

High blood pressure. Porphyrin buildup can damage your kidneys and may result in high blood

pressure (hypertension).

Chronic kidney failure. Porphyrin buildup may cause your kidneys to gradually lose their ability to

function.

Liver damage. Some forms of porphyria cause excessive porphyrins in your liver, which may lead

to severe liver damage that can eventually require a liver transplant.

Permanent skin damage. When your skin heals after cutaneous porphyria, it may have an

abnormal appearance and coloring. Scars may remain on your skin as well, and lasting skin

problems may cause your hair to fall out.

2.9.6 Diagnosis

Many signs and symptoms of porphyria are similar to those of other more common diseases. Also, because

porphyria is rare, it can be more difficult to diagnosis. Lab tests are required to make a definitive diagnosis of

porphyria and to determine which form of the disease you have.

If your doctor suspects porphyria, he or she may recommend these tests:

Urine test. If you have a form of acute porphyria, a urine test may reveal elevated levels of two

substances: porphobilinogen and delta-aminolevulinic acids, as well as other porphyrins.

Blood test. If you have a form of cutaneous porphyria, a blood test may show an elevation in the

level of porphyrins in your blood plasma.

Stool sample test. Analysis of a stool sample may reveal elevated levels of some porphyrins that

may not be detected in urine samples. This test may help your doctor determine your specific

type of porphyria.

More tests may be needed to confirm the type of porphyria you have. Genetic testing may be suggested in the

family of a person with porphyria.

2.9.7 Treatment

Treatment depends on the type of porphyria you have and is directed at relieving symptoms.

Acute porphyrias

Treatment of acute porphyrias focuses on providing rapid treatment of symptoms and preventing

complications. This may require hospitalization in severe cases. Treatment may include:

Stopping medications that may have triggered symptoms

Medication to control pain, nausea and vomiting

Prompt treatment of infections or other illness that may have caused symptoms

Intravenous sugar (glucose) or sugar taken by mouth, if able, to maintain an adequate intake of

carbohydrates

Intravenous fluids to combat dehydration

Injections of hemin, a medication that is a form of heme, to limit the body's production of

porphyrin

Cutaneous porphyrias

Treatment of cutaneous porphyrias focuses on reducing exposure to sunlight and the amount of porphyrins in

your body to help eliminate your symptoms. This may include:

Drawing blood (phlebotomy). Drawing a certain amount of blood from one of your veins reduces

the iron in your body, which decreases porphyrins. You may need to have a phlebotomy repeated

at regular intervals before cutaneous porphyria goes into remission.

Medication. Drugs used to treat malaria — hydroxychloroquine (Plaquenil) or, less often,

chloroquine (Aralen) — can absorb excess porphyrins and help your body get rid of them more

quickly than usual. These medications are generally used only in people who can't tolerate a

phlebotomy.

Beta carotene. Long-term treatment of cutaneous porphyrias may include daily doses of

prescription beta carotene. Beta carotene may increase your skin's tolerance to sunlight. Your

doctor can tell you what kind of beta carotene will work best for porphyria photosensitivity.

Reducing or eliminating triggers. Triggers, such as certain medications or too much sunlight,

which activated the disease, should be reduced or removed if possible, with guidance from your

doctor.

Vitamin D. Supplements may be recommended to replace vitamin D deficiency caused by

avoidance of sunlight.

2.9.8 Prevention

Although there's no way to prevent porphyria, if you have the disease, these steps may help prevent

symptoms:

Avoid medications known to trigger acute attacks. Ask your doctor for a list of safe and unsafe

drugs.

Don't use alcohol or illegal drugs.

Avoid fasting and dieting that involves severe calorie restriction.

Don't smoke.

Minimize sun exposure. When you're outdoors, wear protective clothing and use a broad-

spectrum sunscreen with a high sun protection factor (SPF).

Treat infections and other illnesses promptly.

Take steps to reduce emotional stress.

Because porphyria is an inherited disorder, your siblings and other family members may want to consider

genetic testing to determine if they have the disease.

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http://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/fibrosis-and-

cirrhosis/hepatic-fibrosis

http://www.webmd.com/digestive-disorders/cirrhosis-liver?page=3

http://en.wikipedia.org/wiki/Cirrhosis

http://www.medicinenet.com/liver_cancer_hepatocellular_carcinoma

http://www.nlm.nih.gov/medlineplus/ency/article/000484.htm

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http://www.mayoclinic.org/diseases-conditions/porphyria/basics